The present invention relates to a process for the preparation of methyltrifluoroacetate. Since methyltrifluoroacetate is used as a synthesis intermediate in the pharmaceutical industry, a high purity is often required. The present invention makes it possible to meet this objective.
Previously, as described in Hagen, Miller, Bynum, Kapila 47 Journal of Organic Chemistry 1345-1347 (1982), methyltrifluoroacetate has been prepared by the condensation of trifluoroacetic acid with methanol followed by a simple distillation. The process achieves an ester yield of 100% having a boiling point of 49.degree.-51.degree. C. However, in view of the fact that the boiling point of the pure methyl ester of trifluoroacetic acid is 41.degree.-43.degree. C. (Beilstein E IV-2 p. 463), the product obtained by the process in this article cannot consist of pure methyltrifluoroacetate.
The art also discloses the preparation of trifluoroacetic acid esters by reacting an alcohol with an excess of trifluoroacetic acid in the presence of a catalyst of sulfuric acid. The ester is then washed with water. Moffat and Hunt, 79 Journal of the American Chemical Society 54 (1957) and 81 Journal of the American Chemical Society 2082-86 (1959). During the washing of the ester with water, a partial hydrolysis takes place and, hence, the excess trifluoroacetic acid and the products of hydrolysis are highly diluted in the aqueous medium. As a result, they can only be recovered for industrial use with great difficulty. These two drawbacks render this process industrially unexploitable, especially from an economic point of view, because the starting raw materials, especially trifluoroacetic acid, are very expensive.
Research Disclosure No. 299,359 discloses the condensation of trifluoroacetic acid with an aliphatic alcohol containing a short alkyl chain in the presence of a catalytic quantity of a strong mineral acid. The organic phase is then treated with a strong mineral acid and, finally, distilled to obtain the ester. In this process, the trifluoroacetic acid and the alcohol are used in approximately equimolar quantities.
When a small excess, such as 5%, of methanol relative to the quantity of trifluoroacetic acid is used in the preparation of methyltrifluoroacetate, in the presence of large quantities of sulfuric acid, the yield of the esterification reaction is not quantitative. When catalytic quantities of sulfuric acid are employed, water is distilled with the ester. This gives rise to a slight hydrolysis with the formation of trifluoroacetic acid that cannot be recovered. If a larger excess of methanol is used, pure methyltrifluoroacetate cannot be separated, because of the existence of an azeotrope of methyltrifluoroacetate and methanol. If an excess of trifluoroacetic acid relative to methanol is used, either the excess added is lost, which is not very useful from an economic point of view in view of the price of trifluoroacetic acid, or a very complicated recovery process must be developed because trifluoroacetic acid forms an azeotrope with water.
Thus, none of these previous processes makes it possible to manufacture methyltrifluoroacetate in an industrially viable manner.